Radiographic abnormalities in Rothmund-Thomson syndrome and genotype-phenotype correlation with RECQL4 mutation status.

OBJECTIVE: The purpose of this study was to summarize the radiographic skeletal findings in patients with Rothmund-Thomson syndrome (RTS) and to determine whether there is an association between the presence of skeletal abnormalities and the mutational status of the RECQL4 gene. SUBJECTS AND METHODS: Twenty-eight subjects with RTS underwent skeletal surveys and RECQL4 DNA mutation testing. Radiographs were reviewed by two radiologists. RECQL4 mutation testing by DNA sequencing of the gene was performed by a diagnostic laboratory. Genotype-phenotype analysis by Fisher's exact test was performed to investigate whether there was a correlation between mutation status and skeletal abnormalities. RESULTS: Twenty-one (75%) of the subjects had at least one significant skeletal abnormality, the more common being abnormal metaphyseal trabeculation, brachymesophalangy, thumb aplasia or hypoplasia, osteopenia, dislocation of the radial head, radial aplasia or hypoplasia, and patellar ossification defects. Three subjects had a history of destructive bone lesion (osteosarcoma). Genotype-phenotype analysis showed a significant correlation between RECQL4 mutational status and the presence of skeletal abnormalities (p < 0.0001). CONCLUSION: Skeletal abnormalities are frequent in persons with RTS. Many of these abnormalities are not clinically apparent but are detectable on radiographs. The presence of skeletal abnormalities correlates with RECQL4 mutation status, which has been found to correlate with risk of osteosarcoma. Skeletal surveys aid in both diagnosis and management of RTS.

Kindler syndrome.

Kindler syndrome is a rare genodermatosis characterized by acral bullae and photosensitivity. The photosensitivity improves with advancing age and results in progressive poikiloderma and cutaneous atrophy, and many additional features have also been described. This report describes two male Kindler syndrome patients with classical features of acral blistering and photosensitivity in childhood, and subsequent development of poikiloderma, leukokeratosis of oro-ano-genital mucosae, phimosis and meatal stenosis. The first patient had additional ophthalmic features of chronic simple conjunctivitis caused by persistent irritation, multiple stromal nebular corneal opacities and thickened corneal nerves. The second patient showed skeletal changes, namely a dome-shaped skull (turri-cephaly), bifid fourth rib, missing fifth rib, short fourth and fifth metacarpals and mandibular abnormalities. This is the first report of such ophthalmic and skeletal features of Kindler syndrome.

[Rothmund-Thomson syndrome and osteosarcoma]. / Rothmund-Thomson-Syndrom und Osteosarkom.

Until now less than 200 cases of Rothmund Thomson syndrome (RTS) also called Poikiloderma atrophicans have been reported. RTS is an autosomal recessive dermatosis characterized by athropy and teleangiectasia of the skin, juvenile cataract, hypogonadism and sceletal abnormalities. These osseous disorders include cortical hyperostosis mimicking rickets or chondrodysthropy and may mask early signs of malignant disorders. This seems to be a problem due to the fact that there is an association between osteosarcoma and RTS. The radiologic findings of both RTS and osteosarcoma in a 7 year old female are discussed.

Instability of lymphocyte chromosomes in a girl with Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome is a rare autosomal recessive syndrome characterised by poikiloderma of the face and extremities, alopecia, short stature, and skeletal defects. We report a patient with the characteristic features of Rothmund-Thomson syndrome who also had lymphocyte chromosome abnormalities. She has a small flat face with short palpebral fissures and micrognathia together with severe skeletal abnormalities of the upper extremities with absence of both radii, short dysmorphic ulnae, a rudimentary right thumb, and aplasia of the left thumb. She also has anal atresia with a rectovaginal fistula. From the age of 3 months she developed poikiloderma skin changes on the face and extensor surfaces of the extremities. Mental development seems to be normal. Lymphocyte chromosomes in the neonatal period showed an unidentified marker chromosome in eight of a total of 32 cells. A repeat analysis at the age of 10 months showed three abnormal cells out of 100 analysed: 47,XX,-7,+i(7q),+7p, 46,XX,t(3;18)(p14.2;q22), and 49,XX,+del(3)(p11.2),+mar,+mar. A skin biopsy from an affected area showed poor growth and five of 48 cells analysed had structural abnormalities. The father had one of 48 cells with an additional marker chromosome and two cells with different 7;14 translocations. The abnormal chromosome complements in lymphocytes indicate that there may be in vivo chromosome instability in Rothmund-Thomson syndrome.

Rothmund-Thomson syndrome and osteosarcoma.

A 10-year-old girl with Rothmund-Thomson syndrome developed a fibular osteosarcoma. Standard chemotherapy produced intolerable toxicity, necessitating a modification of therapy. Initial DNA repair studies on skin fibroblasts were abnormal, but repeat studies failed to reproduce the defects.

Osteosarcoma in a boy with Rothmund-Thomson syndrome.

The first case of osteosarcoma in a 13 year old boy with Rothmund-Thomson syndrome is reported. The association between these two conditions is uncertain.